To test the hypothesis that higher habitual intake of fructose from regular food sources (assessed as total fructose, fructose from fruits, fructose from juices, and fructose from sugar-sweetened beverages (SSB)) are associated with lower hepatic but not peripheral insulin sensitivity and higher fatty liver index (FLI) in patients with recently diagnosed T2D, as well as those without diabetes (CON).

Background:

There is increasing concern that dietary fructose may be a key contributor to the rising prevalence of metabolic disorders.

Fructose intake may specifically affect the liver due to its mainly hepatic metabolism.

As indicated in previous studies, the effect of fructose intake on hepatic insulin sensitivity and hepatocellular fat content seems to depend on its energy contribution to the diet, although these findings are inconsistent.

The role of moderate or high fructose intake, as well as its source, on peripheral insulin sensitivity remains uncertain.

Methods:

Participants were recruited from the ongoing German Diabetes Study (GDS; clinicaltrials.gov:NCT01055093), a prospective observational cohort study investigating the natural history of diabetes and the development of diabetes-related comorbidities.

Patients with T2D and CON were included consecutively between August 2012 and June 2016, if they provided data on their habitual food intake and underwent the hyperinsulinemic -eugylcemic clamp test. In total, 223 participants (161 patients with recently diagnosed T2D and 62 CON) were included in the analyses.

Habitual dietary intake was assessed using the semi-quantitative food frequency questionnaire (FFQ), which was designed and validated within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study. The EPIC-FFQ asks for usual food consumption frequencies of 148 food items within the last twelve months, for an average portion size. The main sources of fructose investigated in the questionnaire are fruits, SSB, vegetables, juices, sugar and confectionary, cake, and alcoholic beverages.

Mean total daily energy (TEI) (MJ/day) and fructose (g/day) intake was derived for each participant. For the present analysis, fructose intake (g/day) was considered as sucrose plus non-sucrose bound fructose and as non-sucrose bound fructose intake, and further differentiated into total fructose intake, fructose intake from fruits, fructose intake from juices, and fructose intake from SSB.

Findings:

While total carbohydrate, disaccharide, sucrose and sucrose plus non-sucrose bound fructose intake was higher among CON compared to T2D, total non-sucrose bound fructose intake was comparable between groups.

Sucrose plus non-sucrose bound fructose intake from fruits accounted for about 29% of total fructose intake, while fructose intake from SSB accounted for about 10% and fructose intake from juices for about 8% of total fructose intake in this cohort.

Among patients with T2D, each doubling of sucrose plus non-sucrose bound fructose intake from fruits at a constant TEI level was related to a reduction in the odds of having a fatty liver by 13%. For non-sucrose bound fructose intake, this association was slightly attenuated after adjustment for the parameters of physical activity (odds of having a fatty liver was reduced by 11%).

Each doubling of sucrose plus non-sucrose bound and of non-sucrose bound fructose intake from SSB was associated with an increase in the odds of having a fatty liver based on the FLI by 16% and 17% among individuals with T2D, respectively. Intake of sucrose plus non-sucrose bound as well as of non-sucrose bound total fructose and of fructose from fruit juices was not independently associated with FLI.

Conclusions:

The present study indicates that intake of fructose from SSB appears to have a detrimental effect on peripheral and hepatic insulin sensitivity, even when consumed in very moderate daily amounts. By contrast, fruit-derived fructose was not related to unfavorable metabolic effects and even showed inverse associations with the hepatocellular fat content of individuals with T2D.

Points to Consider:

The findings of this study are limited by its observational design. Further, there was a smaller number of CON compared to patients with T2D.

Residual confounding by e.g., dietary or lifestyle factors associated with the consumption of fruits, juices, and specifically SSB, needs to be considered when interpreting the present findings.

Hepatocellular fat content was assessed by the FLI rather than by magnetic resonance spectroscopy.

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